Ex vivo pharmacokinetic/pharmacodynamic of hexahydrocolupulone against Clostridium perfringens in broiler chickens

TL;DR

This study examines how hexahydrocolupulone fights Clostridium perfringens in broiler chickens and determines the best dosage for treatment.

Contribution

The study introduces a dosing regimen for hexahydrocolupulone based on PK/PD modeling in broiler chickens.

Findings

Hexahydrocolupulone's MIC against C. perfringens ranged from 2 to 16 mg/L in broth and 8 to 64 mg/L in ileal content.

A dosage of 32.9 mg/kg every 24 hours for 3 days is effective if MIC is below 4 mg/L.

The AUC0-24h/MIC values for bacteriostatic, bactericidal, and eradication effects were 36.79, 52.67, and 62.71 hours, respectively.

Abstract

The economic impact of necrotizing enteritis (NE) resulting from Clostridium perfringens infection has been significant within the broiler industry. This study primarily investigated the antibacterial efficacy of hexahydrocolupulone against C. perfringens, and its pharmacokinetics within the ileal contents of broiler chickens. Additionally, a dosing regimen was developed based on the pharmacokinetic/pharmacodynamic (PK/PD) model specific to broiler chickens. Results of the study indicated that the minimum inhibitory concentration (MIC) of hexahydrocolupulone against C. perfringens ranged from 2 mg/L to 16 mg/L in MH broth. However, in ileal content, the MIC ranged from 8 mg/L to 64 mg/L. The mutation prevention concentration (MPC) in the culture medium was found to be 128 mg/L. After oral administration of hexahydrocolupulone at a single dosage of 10–40 mg/kg bodyweight, the peak concentration (Cmax), maximum concentration time (Tmax), and area under the concentration-time curve (AUC) in ileal content of broiler chickens were 291.42–3519.50 μg/g, 1–1.5 h, and 478.99–3121.41 μg h/g, respectively. By integrating the in vivo PK and ex vivo PD data, the AUC0-24h/MIC values required for achieving bacteriostatic, bactericidal, and bacterial eradication effects were determined to be 36.79, 52.67, and 62.71 h, respectively. A dosage regimen of 32.9 mg/kg at 24 h intervals for a duration of 3 days would yield therapeutic efficacy in broiler chickens against C. perfringens, provided that the MIC below 4 mg/L.

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